Biology subjects

Gilbert, J.

Publications and source records attributed to Gilbert, J..

At least 19 recordsLinked to original sources

bioRxiv2026

Type 2B VWD substitutions trigger enhanced macrophage-mediated clearance that is attenuated by the BT200 aptamer

Type 2B von Willebrand disease (VWD) is characterized by missense variants in exon 28 of the von Willebrand factor (VWF) gene that encodes the VWF-A1 domain. These missense mutations result in single amino acid residue substitutions that cause activation of VWF-A1 and promote spontaneous interaction with platelet GPIba;. Importantly, enhanced VWF clearance has been shown to play a key pathogenic role in >90% patients with Type 2B VWD. Although this VWF clearance occurs via mechanisms that are independent of VWF-platelet complex formation, the biological mechanisms responsible for the increased clearance of type 2B VWD variants remain poorly understood. In this study, we investigated a series of different type 2B amino acid substitutions within the VWF-A1 domain (R1306W, R1308C, W1313C and R1379L). We demonstrate that these variants all exhibit significantly increased macrophage binding. In part, the enhanced macrophage interactions are mediated via increased binding of type 2B VWD variants to LRP1 extracellular cluster II and IV. Our findings further demonstrate that the K1405-K1408 lysine cluster in the VWF-A1 domain plays a key role in enabling enhanced LRP1 interactions for type 2B VWD variants. In addition, we show that type 2B VWF variants demonstrate significantly enhanced interaction with the macrophage MGL receptor. Finally, and importantly from a clinical perspective, we demonstrate that the increase in macrophage binding for type 2B variants is significantly attenuated in the presence of BT200. Collectively, our findings have direct translational relevance with respect to the clinical heterogeneity and treatment of type 2B VWD.

biochemistry↗

bioRxiv2026

Social microbiome transmission predicts microbial specialization and host lifespan in a wild primate

Social interactions are proposed to provide reliable routes for microbial transmission between animals, facilitating animal-microbiome co-evolution. However, microbiome transmission remains challenging to measure in wild populations. Here we combine behavioral observations of wild baboons with repeated strain-resolved metagenomic profiling to identify individual gut microbial species that follow a dominant mode of social transmission. In an 18-year metagenomic time series from the same population, baboons with higher levels of socially transmitted species lived longer than those with lower levels of socially transmitted species. Socially transmitted species were also more stable and persistent within baboons, yet had narrower host ranges outside of baboons. Thus, social transmission is not only detectable in free-living primates, but may play a special role in both host and microbial fitness.

evolutionary biology↗

bioRxiv2026

Human-specific multicopy gene FRMPD2 promotes synapse formation via recruitment of neuroligin 1

FRMPD2 is a human-specific multi-copy gene with higher mRNA expression in brain tissue, but its role in synapse formation and neurodevelopment remains unknown. We find that FRMPD2 is a neuron-specific protein with a high expression level in human brains compared to rodent brains. FRMPD2 overexpression in rat neurons stimulates synaptogenesis, leading to increased synaptic activities. Importantly, our results show that FRMPD2 via its PDZ domains recruits and enhances neuroligin-1 protein levels at the postsynaptic sites, and via its FERM domain interacts with the F-actin network in the spine. Increased expression of FRMPD2 also promotes spine formation and maturation, a foundational process for synapse formation. In developing embryonic mouse brains expressing higher FRMPD2 protein levels, we observed delayed neuronal migration, presumably promoting a protracted timeline for cortical lamination as a feature in human brain development. Behaviorally, mice with FRMPD2 overexpression in the brain demonstrate enhanced spatial memory retention. These findings indicate an important function for FRMPD2 in neuronal connectivity, brain development, and cognitive function.

neuroscience↗

bioRxiv2026

Identifying Robust Subclonal Structures through Tumor Progression Tree Alignment

Understanding and comparing tumor evolutionary histories is fundamental to cancer genomics. Clonal trees, used to model tumor progression, are rooted, unordered trees in which each node represents a subclone labeled by a set of distinct mutations. To compare two clonal trees, we introduce omlta, the optimal multi-label tree alignment, which removes the minimum number of mutation labels from the trees, so that the remaining trees are isomorphic. Computing omlta is NP-hard. Here, we present an algorithm to compute the omlta, with a running time of [Formula] where L [≥] 1 is the total number of mutation labels occurring in the input trees and k is the minimum possible number of mutation labels that need to be removed for the alignment. Our implementation (https://github.com/algo-cancer/omlta) is the first computational tool for determining the optimal alignment between clonal trees. We applied omlta to 126 cases from the TRACERx study on non-small cell lung cancers and some melanoma single-cell data.

cancer biology↗

bioRxiv2026

Warming-induced sex bias fuels deceptive conservation success in sea turtles

Global warming threatens species with temperature-dependent sex determination (TSD) by risking extreme offspring sex-ratio bias. In sea turtles, warmer incubation conditions produce more females. Such biases can transiently inflate apparent population growth before male scarcity undermines reproduction, possibly leading to population extinction. Here, we combine 15 years of field monitoring, drone-based sex-ratio surveys, Argos telemetry, and eco-physiological modelling to test whether rising temperatures underpin the rapid increase in loggerhead (Caretta caretta) nesting in Cabo Verde, one of the worlds largest populations. Historical air temperature, lagged by one generation, predicts current nest counts, consistent with a climate-driven, female-biased population. Drone surveys reveal an approximately 9:1 female-to-male breeding sex ratio across two consecutive breeding seasons, and simulations reproduce observed nesting trajectories under historical warming but not under null (no-warming) scenarios. Extending the analysis to 28 global loggerhead populations reveals consistent links between temperatures, latitude, and nesting trends. Our results identify warming-induced sex ratio bias as a key, yet deceptive, driver of apparent recovery, highlighting the need to reassess conservation success through the lens of demography of TSD species.

ecology↗

bioRxiv2025

Oncogene SETDB1s Dual Role in Endometrial Cancer: Driving Tumor Progression and Immune Escape

Oncogene SETDB1, an H3K9 methyltransferase, drives tumorigenesis in various cancers. Using endometrial cancer (EC) as a model, we discovered SETDB1s dual mechanisms in driving EC tumorigenesis and mediating immune evasion. SETDB1 knockout (SETDB1-/-) tumor-bearing mice exhibited prolonged survival of up to 100 days. Transcriptomic profiling of SETDB1-/- EC cells revealed decreased expression of oncogenes (POLR2A, MSH6, FLNA) and increased expression of tumor suppressor genes (PGR, RERG, ZNF582), which indicates that SETDB1 intrinsically promotes EC tumor proliferation by regulating these downstream genes. SETDB1 repressed repeat elements and the interferon pathway, mediating immune evasion extrinsically by inhibiting anti-tumor macrophage infiltration. ChIP-seq analysis showed SETDB1 binding at pericentromeric regions on many chromosomes and numerous ZNFs. Loss of SETDB1 resulted in abnormal cell division. SETDB1-/- tumors displayed reduced proliferation markers (Ki67, pHH3) and increased macrophage infiltration. Mechanistically, SETDB1 promotes CD47 (a dont-eat-me signal) and represses CCL5 and CXCL9 (macrophage and T-cell recruiting chemokines), contributing to immune evasion. M1-like macrophages killed more SETDB1-/- cells in co-culture. Additionally, SETDB1 knockout in mouse EC cells reduced tumor growth in C57BL/6 mice, with increased macrophage and CD4+ T-cell infiltration. Our results indicates that elevated SETDB1 and its target genes can predict higher tumor grade and worse survival, suggesting that targeting SETDB1 could be a promising therapeutic strategy for EC.

cancer biology↗

bioRxiv2024

Gut and oral microbial community characterization from women with breast cancer, women with ductal carcinoma in situ, and healthy women reveals differences in gut but not oral microbiota

This study characterized and compared the fecal and oral microbiota from women with early-stage breast cancer (BC), women with ductal carcinoma in situ (DCIS), and healthy women. Fecal and oral samples were collected from newly diagnosed patients prior to any therapy and characterized using 16S rRNA sequencing. Measures of gut microbial alpha diversity were significantly lower in the BC versus healthy cohort. Beta diversity differed significantly between the BC or DCIS and healthy groups and several differentially abundant taxa were identified. Clustering (non-negative matrix factorization) of the gut microbiota identified 5 bacterial guilds dominated by either Prevotella, Enterobacteriaceae, Akkermansia, Clostridiales, or Bacteroides. The Bacteroides and Enterobacteriaceae guilds were significantly more abundant in the BC cohort compared to healthy controls whereas the Clostridiales guild was more abundant in the healthy group. Finally, prediction of functional pathways identified 23 pathways that differed between the BC and healthy gut microbiota including lipopolysaccharide biosynthesis, glycan biosynthesis and metabolism, lipid metabolism, and sphingolipid metabolism. In contrast to the gut microbiomes, there were no significant differences in alpha or beta diversity in the oral microbiomes and very few differentially abundant taxa were observed. NMF analysis of the oral microbiota samples identified 7 guilds dominated by Veillonella, Prevotella, Gemellaceae, Haemophilus, Neisseria, Propionibacterium, and Streptococcus, however, none of these guilds were differentially associated with the different cohorts. Our results suggest that alterations in the gut microbiota, but not oral microbiota, may provide the basis for interventions targeting the gut microbiome to improve treatment outcomes and long-term prognosis. IMPORTANCEEmerging evidence suggests that the gut microbiota may play a role in breast cancer. Few studies have evaluated both the gut and oral microbiomes in women with breast cancer (BC) and none have characterized these microbiomes in women with ductal carcinoma in situ (DCIS). We surveyed the gut and oral microbiomes from women with BC or DCIS and healthy women and identified compositional and functional features of the gut microbiota that differed between these cohorts. In contrast, very few differential features were identified in the oral microbiota. These findings suggest that the oral microbiome is unlikely to be an effective risk marker for DCIS or breast cancer compared to the gut microbiome. Understanding the role of gut bacteria in BC and DCIS may open up new opportunities for the development of novel markers for early detection (or markers of susceptibility) as well as new strategies for prevention and/or treatment.

microbiology↗

bioRxiv2023

Structural Insights on Ionizable Dlin-MC3-DMA Lipids in DOPC Layers by Combining Accurate Atomistic Force Fields, Molecular Dynamics Simulations and Neutron Reflectivity

Ionizable lipids such as the promising Dlin-MC3-DMA (MC3) are essential for the successful design of lipid nanoparticles (LNPs) as drug delivery agents. Combining molecular dynamics simulations with experimental data such as neutron reflectivity experiments and other scattering techniques is essential to provide insights into the internal structure of LNPs, which is not fully understood to date. However, the accuracy of the simulations relies on the choice of force field parameters and high-quality experimental data is indispensable to verify the parametrization. For MC3, different parameterizations in combination with the CHARMM and the Slipids force field have recently emerged. Here, we complement the existing efforts by providing parameters for cationic and neutral MC3 compatible with the AMBER Lipid17 force field. Subsequently, we carefully assess the accuracy of the different force fields by providing a direct comparison to neutron reflectivity experiments of mixed lipid bilayers consisting of MC3 and DOPC at different pH. At low pH (cationic MC3) and at high pH (neutral MC3) the newly developed MC3 parameters in combination with AMBER Lipid17 for DOPC give good agreement with the experiments. Overall, the agreement is similar compared to the Park-Im parameters for MC3 in combination with the CHARMM36 force field for DOPC. The Ermilova-Swenson MC3 parameters in combination with the Slipids force field underestimate the bilayer thickness. While the distribution of cationic MC3 is very similar, the different force fields for neutral MC3 reveal distinct differences ranging from strong accumulation in the membrane center (current MC3/AMBER Lipid17 DOPC), over mild accumulation (Park-Im MC3/CHARMM36 DOPC) to surface accumulation (Ermilova-Swenson MC3/Slipids DOPC). These pronounced differences highlight the importance of accurate force field parameters and their experimental validation.

biophysics↗

bioRxiv2022

Zika virus-induces metabolic alterations in fetal neuronal progenitors that could influence in neurodevelopment during early pregnancy

Neuronal progenitor subtypes have distinct fate restrictions regulated by time-dependent activation of energetic pathways. Thus, the hijacking of cellular metabolism by Zika virus (ZIKV) to support its replication may contribute to damage in the developing fetal brain. Here, we showed that ZIKV replicates differently in two glycolytically distinct hiPSC-derived neuronal progenitors that correspond to early and late progenitors in the forebrain. This differential replication alters the transcription of metabolic genes and upregulates the glycolytic capacity of progenitor subtypes. Analysis using Imagestream(R) revealed that, during early stages of infection, ZIKV replication in early progenitors increases lipid droplet abundance and decreases mitochondrial size and membrane potential. During later stages infection, early progenitors show increased subcellular distribution of lipid droplets, whilst late progenitors show decreased mitochondria size. The finding that there are hi-NPC subtype-specific alterations of cellular metabolism during ZIKV infection may help to explain the differences in brain damage over each trimester.

neuroscience↗

bioRxiv2022

Universal gut microbial relationships in the gut microbiome of wild baboons

Ecological relationships between bacteria mediate the services that gut microbiomes provide to their hosts. Knowing the overall direction and strength of these relationships within hosts, and their generalizability across hosts, is essential to learn how microbial ecology scales up to affect microbiome assembly, dynamics, and host health. Here we gain insight into these patterns by inferring thousands of correlations in bacterial abundance between pairs of gut microbiome taxa from extensive time series data (5,534 microbiome profiles from 56 wild baboon hosts over a 13-year period). We model these time series using a statistically robust, multinomial logistic-normal modeling framework and test the degree to which bacterial abundance correlations are consistent across hosts (i.e., "universal") or individualized to each host. We also compare these patterns to two publicly available human data sets. We find that baboon gut microbial relationships are largely universal: correlation patterns within each baboon host reflect a mixture of idiosyncratic and shared patterns, but the shared pattern dominates by almost 2-fold. Surprisingly, the strongest and most consistently correlated bacterial pairs across hosts were overwhelmingly positively correlated and typically belonged to the same family--a 3-fold enrichment compared to pairs drawn from the data set as a whole. The bias towards universal, positive bacterial correlations was also apparent in monthly samples from human infants, and bacterial families that had universal relationships in baboons also tended to be universal in human infants. Together, our results advance our understanding of the relationships that shape gut microbial ecosystems, with implications for microbiome personalization, community assembly and stability, and the feasibility of microbiome interventions to improve host health.

ecology↗

bioRxiv2022

Multi-omic analysis along the gut-brain axis points to a functional architecture of autism

Autism is a highly heritable neurodevelopmental disorder characterized by heterogeneous cognitive, behavioral and communication impairments. Disruption of the gut-brain axis (GBA) has been implicated in autism, with dozens of cross-sectional microbiome and other omic studies revealing autism-specific profiles along the GBA albeit with little agreement in composition or magnitude. To explore the functional architecture of autism, we developed an age and sex-matched Bayesian differential ranking algorithm that identified autism-specific profiles across 10 cross-sectional microbiome datasets and 15 other omic datasets, including dietary patterns, metabolomics, cytokine profiles, and human brain expression profiles. The analysis uncovered a highly significant, functional architecture along the GBA that encapsulated the overall heterogeneity of autism phenotypes. This architecture was determined by autism-specific amino acid, carbohydrate and lipid metabolism profiles predominantly encoded by microbial species in the genera Prevotella, Enterococcus, Bifidobacterium, and Desulfovibrio, and was mirrored in brain-associated gene expression profiles and restrictive dietary patterns in individuals with autism. Pro-inflammatory cytokine profiling and virome association analysis further supported the existence of an autism-specific architecture associated with particular microbial genera. Re-analysis of a longitudinal intervention study in autism recapitulated the cross-sectional profiles, and showed a strong association between temporal changes in microbiome composition and autism symptoms. Further elucidation of the functional architecture of autism, including of the role the microbiome plays in it, will require deep, multi-omic longitudinal intervention studies on well-defined stratified cohorts to support causal and mechanistic inference.

microbiology↗

bioRxiv2021

Survival of hatchery grown native oysters is associated with specific gut-associated bacteria at various locations within the Puget Sound

The Olympia oyster (Ostrea lurida) of the Puget Sound suffered a dramatic population crash, but restoration efforts hope to revive this native species. One overlooked variable in the process of assessing ecosystem health is association of bacteria with marine organisms and the environments they occupy. Oyster microbiomes are known to differ significantly between species, tissue type, and the habitat in which they are found. The goals of this study were to determine the impact of field site and habitat on the oyster microbiome and to identify core oyster-associated bacteria in the Puget Sound. Olympia oysters from one parental family were deployed at four sites in the Puget Sound both inside and outside of eelgrass (Zostera marina) beds. Using 16S rRNA gene amplicon sequencing of the oyster gut, shell, surrounding seawater and sediment, we demonstrate that gut-associated bacteria are distinct from the surrounding environment and vary by field site. Furthermore, regional differences in the gut microbiota are associated with the survival rates of oysters at each site after two months of field exposure. However, habitat type had no influence on microbiome diversity. Further work is needed to identify the specific bacterial dynamics that are associated with oyster physiology and survival rates. ImportanceThe outcomes of this study demonstrate the need to monitor microbial ecology at potential oyster restoration sites, specifically for the native Olympia oyster in the Puget Sound. Some areas of Puget Sound may be less amenable to Olympia oyster restoration than others due to microbiome colonization trends. Furthermore, this study puts the oyster microbiome in the context of its surroundings, providing a holistic perspective on the factors that may influence oyster performance and microbial ecology.

microbiology↗

bioRxiv2021

Gestational insulin resistance is mediated by the gut microbiome-indoleamine 2,3-dioxygenase axis

Background and aimsNormal gestation involves reprogramming of maternal gut microbiome (GM) that may contribute to maternal metabolic changes by unclear mechanisms. This study aimed to understand the mechanistic underpinnings of GM - maternal metabolism interaction. MethodsThe GM and plasma metabolome of CD1, NIH-Swiss and C57BL/6J mice were analyzed using 16S rRNA sequencing and untargeted LC-MS throughout gestation and postpartum. Pharmacologic and genetic knockout mouse models were used to identify the role of indoleamine 2,3-dioxygenase (IDO1) in pregnancy-associated insulin resistance (IR). Involvement of gestational GM in the process was studied using fecal microbial transplants (FMT). ResultsSignificant variation in gut microbial alpha diversity occurred throughout pregnancy. Enrichment in gut bacterial taxa was mouse strain and pregnancy time-point specific, with species enriched at gestation day 15/19 (G15/19), a point of heightened IR, distinct from those enriched pre- or post- pregnancy. Untargeted and targeted metabolomics revealed elevated plasma kynurenine at G15/19 in all three mouse strains. IDO1, the rate limiting enzyme for kynurenine production, had increased intestinal expression at G15, which was associated with mild systemic and gut inflammation. Pharmacologic and genetic inhibition of IDO1 inhibited kynurenine levels and reversed pregnancy-associated IR. FMT revealed that IDO1 induction and local kynurenine levels effects on IR derive from the GM in both mouse and human pregnancy. ConclusionsGM changes accompanying pregnancy shift IDO1-dependent tryptophan metabolism toward kynurenine production, intestinal inflammation and gestational IR, a phenotype reversed by genetic deletion or inhibition of IDO1.

physiology↗

bioRxiv2021

OGUs enable effective, phylogeny-aware analysis of even shallow metagenome community structures

We introduce Operational Genomic Unit (OGU), a metagenome analysis strategy that directly exploits sequence alignment hits to individual reference genomes as the minimum unit for assessing the diversity of microbial communities and their relevance to environmental factors. This approach is independent from taxonomic classification, granting the possibility of maximal resolution of community composition, and organizes features into an accurate hierarchy using a phylogenomic tree. The outputs are suitable for contemporary analytical protocols for community ecology, differential abundance and supervised learning while supporting phylogenetic methods, such as UniFrac and phylofactorization, that are seldomly applied to shotgun metagenomics despite being prevalent in 16S rRNA gene amplicon studies. As demonstrated in one synthetic and two real-world case studies, the OGU method produces biologically meaningful patterns from microbiome datasets. Such patterns further remain detectable at very low metagenomic sequencing depths. Compared with taxonomic unit-based analyses implemented in currently adopted metagenomics tools, and the analysis of 16S rRNA gene amplicon sequence variants, this method shows superiority in informing biologically relevant insights, including stronger correlation with body environment and host sex on the Human Microbiome Project dataset, and more accurate prediction of human age by the gut microbiomes in the Finnish population. We provide Woltka, a bioinformatics tool to implement this method, with full integration with the QIIME 2 package and the Qiita web platform, to facilitate OGU adoption in future metagenomics studies. ImportanceShotgun metagenomics is a powerful, yet computationally challenging, technique compared to 16S rRNA gene amplicon sequencing for decoding the composition and structure of microbial communities. However, current analyses of metagenomic data are primarily based on taxonomic classification, which is limited in feature resolution compared to 16S rRNA amplicon sequence variant analysis. To solve these challenges, we introduce Operational Genomic Units (OGUs), which are the individual reference genomes derived from sequence alignment results, without further assigning them taxonomy. The OGU method advances current read-based metagenomics in two dimensions: (i) providing maximal resolution of community composition while (ii) permitting use of phylogeny-aware tools. Our analysis of real-world datasets shows several advantages over currently adopted metagenomic analysis methods and the finest-grained 16S rRNA analysis methods in predicting biological traits. We thus propose the adoption of OGU as standard practice in metagenomic studies.

bioinformatics↗

bioRxiv2019

Plugging the hunger gap: Organic farming supports more abundant nutritional resources for bees at critical periods

O_LIUnderstanding the decline in bee populations and their plant mutualists is of paramount concern for ecosystem health, as well as our future food security. Intensive farming practices are one of the major drivers behind such declines. Organic farming is one of the principal alternatives to conventional practices yet the evidence for its effects are mixed, with some studies showing limited benefits. C_LIO_LIWe conducted bee and floral surveys on 10 paired organic and conventional farms across Yorkshire, UK, to investigate how farming practice influenced the abundance, richness and community composition of bees and flowering plants. C_LIO_LIFirstly, we found that species richness for flowering plants and bees was similar across organic and conventional farms. Floral composition differed between organic and conventional farms with the greatest differences seen in May and June, whereas bee community composition was similar among farming practices. C_LIO_LISecondly, both bee and floral abundance were higher in organic farms. Peaks in floral abundance, and corresponding bee abundance, occurred in particular months, most notably in July, with abundance during the rest of the season being similar across both farming practices. C_LIO_LISynthesis and applications: Our results suggest that higher floral availability on organic farms corresponds with increased bee abundance. Of particular importance was the higher floral abundance during spring, in the pollinator hungry gap, where floral resources are traditionally scarce. However, conventional farms performed comparably to organic farms across the rest of the season, as well as showing similar levels of species richness, diversity and species composition for both flowering plants and bees. We suggest that targeted management on conventional farms, aimed at boosting floral abundance in the spring, when floral abundance is low, could allow conventional farms to make up the shortfall. Additionally, focusing on increasing the diversity of flowering plants, in terms of both phenology and nutritional composition, for both adult bees and their larvae, could improve bee community diversity across both farming systems. C_LI

ecology↗

bioRxiv2019

Parental care shapes evolution of aposematism and provides lifelong protection against predators

Social interactions within species can modulate the response to selection and determine the extent of evolutionary change. Yet relatively little work has determined whether the social environment can influence the evolution of traits that are selected by interactions with other species - a major source of natural selection. Here we show that the amount of parental care received as an offspring can influence the expression, and potential evolution, of warning displays deployed against predators in adulthood. In theory, warning displays by prey are selected by predators for uniformity and to reliably advertise the extent to which individuals are chemically defended. However, the correlated evolution of intensity of the visual display and strength of the chemical defense is only possible if there is a genetic correlation between them. Adult burying beetles Nicrophorus vespilloides bear bright orange elytral markings which advertise their chemical defenses. We experimentally manipulated the level of maternal care that individuals received when they were larvae and then measured the strength of the correlation between the component parts of the warning display when they reached adulthood. We found that under limited care individuals were smaller and produced less conspicuous warning displays. The underlying family (genetic) correlation between the visual display and the chemical defense was weaker in individuals that received little care as larvae. We conclude that parenting by burying beetles modulates the evolvability of aposematic defense, making correlated evolutionary change in signal intensity and chemical defense less likely when they restrict care to their young.\n\nSignificance StatementParental care can improve early offspring survival against predators. However, we have little knowledge of how its effects shape the evolution of predator-prey interactions later in the offsprings life. We tested this with carrion beetles who provide care for offspring and who carry warning coloration to advertise to predators that they are chemically defended. We show that more parental care resulted in larger, more brightly coloured and chemically defended adult beetles. Furthermore, when parents had provided little care for their young we found weaker genetic correlations between warning signal salience and chemical defense. Over time, this could result in untrustworthy warning signals, which could render them ineffective against predators.

evolutionary biology↗

bioRxiv2018

A simple microbiome in esophagus and gills of the European common cuttlefish, Sepia officinalis

The European common cuttlefish, Sepia officinalis, is used extensively in biological and biomedical research yet its microbiome remains poorly characterized. We analyzed the microbiota of the digestive tract, gills, and skin in mariculture-raised S. officinalis using a combination of 16s rRNA amplicon sequencing and fluorescence spectral imaging. Sequencing revealed a highly simplified microbiota consisting largely of two single bacterial amplicon sequence variants (ASVs) of Vibrionaceae and Piscirickettsiaceae. The esophagus was dominated by a single ASV of the genus Vibrio. Imaging revealed a striking organization of bacteria distributed in a discrete layer that lines the esophagus. Imaging with specific probes confirmed the identity of these bacteria as Vibrionaceae. This Vibrio was also abundant in the microbiota of the stomach, cecum, and intestine, but occurred at lower density and in the lumen rather than in a discrete layer; it was present in only trace proportions in tank water and in the microbiome of shrimp that were used as feed for the cuttlefish. These Vibrio were resilient to treatment of animals with the commonly-used antibiotic, enrofloxacin. The gills were colonized by a single ASV in the family Piscirickettsiaceae, which imaging visualized as small clusters of cells. We conclude that bacteria belonging to the Gammaproteobacteria, especially Vibrionaceae, are the major symbionts of the cuttlefish Sepia officinalis cultured from eggs in captivity, and that the esophagus and gills are major colonization sites.\n\nIMPORTANCEMicrobes can play critical roles in the physiology of their animal hosts, as evidenced in cephalopods by the role of Vibrio (Aliivibrio) fischeri in the light organ of the bobtail squid and the role of Alpha- and Gammaproteobacteria in the reproductive system and egg defense in a variety of cephalopods. We sampled the cuttlefish microbiome throughout the digestive tract, gills, and skin and found dense colonization of an unexpected site, the esophagus, by a microbe of the genus Vibrio, as well as colonization of gills by Piscirickettsiaceae. We found these associations to be resilient to the treatment of animals with a common antibiotic, enrofloxacin. This finding expands the range of organisms and body sites known to be associated with Vibrio and is of potential significance for understanding host-symbiont associations as well as for understanding and maintaining the health of cephalopods in mariculture.

microbiology↗

bioRxiv2018

Multiple laboratory mouse reference genomes define strain specific haplotypes and novel functional loci

The most commonly employed mammalian model organism is the laboratory mouse. A wide variety of genetically diverse inbred mouse strains, representing distinct physiological states, disease susceptibilities, and biological mechanisms have been developed over the last century. We report full length draft de novo genome assemblies for 16 of the most widely used inbred strains and reveal for the first time extensive strain-specific haplotype variation. We identify and characterise 2,567 regions on the current Genome Reference Consortium mouse reference genome exhibiting the greatest sequence diversity between strains. These regions are enriched for genes involved in defence and immunity, and exhibit enrichment of transposable elements and signatures of recent retrotransposition events. Combinations of alleles and genes unique to an individual strain are commonly observed at these loci, reflecting distinct strain phenotypes. Several immune related loci, some in previously identified QTLs for disease response have novel haplotypes not present in the reference that may explain the phenotype. We used these genomes to improve the mouse reference genome resulting in the completion of 10 new gene structures, and 62 new coding loci were added to the reference genome annotation. Notably this high quality collection of genomes revealed a previously unannotated gene (Efcab3-like) encoding 5,874 amino acids, one of the largest known in the rodent lineage. Interestingly, Efcab3-like-/- mice exhibit severe size anomalies in four regions of the brain suggesting a mechanism of Efcab3-like regulating brain development.

genomics↗